Even before the advent of AIDS homosexual men were known to be at high risk for anal cancer. Recently the incidence of anal cancer among never married men in the San Francisco area has been reported to be seven times higher than prior to 1980. Since Dialing et al estimated the incidence of anal cancer among homosexual men prior to AIDS to be from 12.5 to 36.9/100,000; the incidence of anal cancer among HIV infected men presently could now be as high as 258/100,000, i.e. approaching that of breast cancer in females. In our ongoing cross-sectional study of anal squamous intraepithilial lesions (ASIL), HIV, HPV, and immunosuppression (CA50738), we find ASIL to be extremely common, especially among HIV-infected men. High grade (HG) , ASIL is common even among only moderately immunosuppressed HIV-infected men. Little is known about the development and natural history of ASIL in men with or without immunosuppression. In a separate (CA-34493) study of cervical SIL (CSIL), we found that 40% of women living without HIV with low grade (LG) CSIL developed HGCSIL within 2-1/2 years, with development of HGCSIL associated with HPV type. Some reports suggest that among iatrogenically immunosuppressed patients, the transit time from LGSIL to HGSIL is accelerated and that HPV types not normally associated with malignancy are seen in HGSIL and cancer. We postulate that HIV-seropositive men are at greater risk for development and progression to high grade lesions than are HIV-seronegative men. We are proposing a four year longitudinal study, (including three years of follow-up) among homosexual men with and without HIV infection to describe and compare the development and natural history of ASIL, and to examine the role of specific HPV types and immunosuppression in the pathogenesis of these lesions. We will enroll 380 HIV seropositive men (1/3 with CD4 counts less than 200, 1/3 between 200-500 and 1/3 greater than 500), and 190 HIV-seronegative men. At each visit, subjects will undergo a standardized interview, general physical exam, detailed genital exam with anal colposcopy, collection of anal samples for HPV DNA, and collection of blood for CD4 subsets and for serologic ASIL will be biopsied and referred for treatment. An understanding of the development and natural history of ASIL and its relationship to HIV, immunosuppression to guide the formulation of strategies for the management detect lesions. In addition, the knowledge gained in this study may further our understanding of the natural history of CSIL in HIV infected women.